Antitumor Immunity Produced by the Liver Kupffer Cells, NK Cells, NKT Cells, and CD8+ CD122+ T Cells

Mouse and human livers contain innate immune leukocytes, NK cells, NKT cells, and macrophage-lineage Kupffer cells. Various bacterial components, including Toll-like receptor (TLR) ligands and an NKT cell ligand (α-galactocylceramide), activate liver Kupffer cells, which produce IL-1, IL-6, IL-12, and TNF. IL-12 activates hepatic NK cells and NKT cells to produce IFN-γ, which further activates hepatic T cells, in turn activating phagocytosis and cytokine production by Kupffer cells in a positive feedback loop. These immunological events are essentially evoked to protect the host from bacterial and viral infections; however, these events also contribute to antitumor and antimetastatic immunity in the liver by activated liver NK cells and NKT cells. Bystander CD8+CD122+ T cells, and tumor-specific memory CD8+T cells, are also induced in the liver by α-galactocylceramide. Furthermore, adoptive transfer experiments have revealed that activated liver lymphocytes may migrate to other organs to inhibit tumor growth, such as the lungs and kidneys. The immunological mechanism underlying the development of hepatocellular carcinoma in cirrhotic livers in hepatitis C patients and liver innate immunity as a double-edged sword (hepatocyte injury/regeneration, septic shock, autoimmune disease, etc.) are also discussed

Airborne microorganisms in the indoor environment of Syowa Station in Antarctica

Airborne bacterial and fungal numbers in the buildings of Syowa Station in Antarctica were examined for 9 months in 2001. The number of bacteria or fungi was less than 20 or 70/m^3 in the dining room and washroom. The average number of bacteria or fungi was less than 1/50 or 1/5 of those in Japan and Europe, respectively, and remained constant regardless of season. The number of airborne microorganisms appeared to depend on drying of the indoor environment by the use of air-conditioners

Role of Kupffer Cells in Systemic Anti-Microbial Defense

The liver has long been recognized as important in digestion. However, the liver’s abundance of innate immune cells strongly suggests that it has specific defense mechanisms. A characteristic anatomical feature of the liver is its large blood flow. The blood flowing out from the whole alimentary tract is transported to the liver via the portal vein and distributed to peripheral structures called sinusoids. Kupffer cells, a typical example of resident macrophages, are located in sinusoids and are in continuous contact with various portal blood components. They have vigorous phagocytic activity and eliminate bacteria coming from the gut before they enter systemic circulation. Based on this framework, Kupffer cells were considered a filter for portal blood pathogens. However, recent evidence reveals that they exert crucial functions in systemic host defense against bacterial infection. To defend against various sources of bacterial pathogens, Kupffer cells construct an efficient surveillance system for systemic circulation, cooperating aggressively with other immune cells. They collaborate with non-immune cells such as hepatocytes and platelets to potentiate defense function. In conclusion, Kupffer cells coordinate immune cell activity to efficiently defend against infections, making them crucial players in systemic antibacterial immunity

Fibulin-4 and -5, but not Fibulin-2, are Associated with Tropoelastin Deposition in Elastin-Producing Cell Culture

Elastic system fibers consist of microfibrils and tropoelastin. During development, microfibrils act as a template on which tropoelastin is deposited. Fibrillin-1 is the major component of microfibrils. It is not clear whether elastic fiber-associated molecules, such as fibulins, contribute to tropoelastin deposition. Among the fibulin family, fibulin-2, -4 and -5 are capable of binding to tropoelastin and fibrillin-1. In the present study, we used the RNA interference (RNAi) technique to establish individual gene-specific knockdown of fibulin-2, -4 and -5 in elastin-producing cells (human gingival fibroblasts; HGF). We then examined the extracellular deposition of tropoelastin using immunofluorescence. RNAi-mediated down-regulation of fibulin-4 and -5 was responsible for the diminution of tropoelastin deposition. Suppression of fibulin-5 appeared to inhibit the formation of fibrillin-1 microfibrils, while that of fibulin-4 did not. Similar results to those for HGF were obtained with human dermal fibroblasts. These results suggest that fibulin-4 and -5 may be associated in different ways with the extracellular deposition of tropoelastin during elastic fiber formation in elastin-producing cells in culture

Altered expression of inflammatory cytokines in primary osteoarthritis by human T lymphotropic virus type I retrovirus infection: a cross-sectional study

Human T cell leukaemia virus type I (HTLV-I) is known to be involved in late-onset chronic polyarthritis as HTLV-I-associated arthropathy. However, it is unclear whether HTLV-I infection could modify the pathophysiology of osteoarthritis (OA). In this study we compared several inflammatory cytokines, such as C-terminal parathyroid hormone-related peptide (C-PTHrP), soluble interleukin-2 receptor (sIL-2R) and interleukin (IL)-6, and an osteo-destruction marker, deoxypyridinoline, in synovial fluid (SF) samples obtained from 22 HTLV-I carriers and 58 control non-carrier patients with OA. These patients were diagnosed clinically and radiographically with primary OA affecting one or both knee joints, and were similar with regard to age, sex and clinical symptoms. We also performed histopathological examination as well as immunohistochemistry of HTLV-I-derived Tax protein in eight synovial tissues taken from carrier patients. C-PTHrP in SF was significantly higher in HTLV-I carriers (287 ± 280 pM) than in non-carriers (69 ± 34 pM), and the concentration in 13 carriers was above the upper range of OA. In HTLV-I carriers, the concentrations of sIL-2R (741 ± 530 IU/ml), IL-6 (55 ± 86 ng/ml) and deoxypyridinoline (3.1 ± 1.8 nM) were higher than in non-carriers (299 ± 303, 2.5 ± 4.0, 0.96 ± 1.0, respectively), and correlated positively with C-PTHrP. C-PTHrP, sIL-2R and IL-6 concentrations in SF positive for IgM antibody against HTLV-I antigen, a marker of persistent viral replication, were higher than of IgM-negative SF. Histologically, five and two synovia showed mild and moderate synovial proliferation with or without some degree of inflammatory reaction, respectively, and could not be distinguished from OA. Tax-positive synoviocytes were observed sparsely in all samples, and often appeared frequently in actively proliferating regions. Our results suggest that although HTLV-I infection does not necessarily worsen the clinical outcome and local synovitis, the virus can potentially modify the pathophysiology of OA by increasing the inflammatory activity in a subset of carrier patients, especially those with IgM antibody. Longitudinal studies are required to assess the association between HTLV-I infection and OA

ナンキョク ショウワキチ ナイ ノ セイブツ キゲン エアロゾル

南極昭和基地建物内における空気中の細菌及び糸状菌数濃度を2001年の9カ月にわたり調査した.食堂及び洗面所において,細菌数濃度は20 CFU/m^3,糸状菌数濃度は70 CFU/m^3 よりも少なかった.また,細菌及び糸状菌の日本やヨーロッパにおける平均値と比較するとそれぞれ1/50及び1/5であり,かつ季節的な変動は見られなかった.従って,昭和基地における空気中の微生物数は,室内の空調による内部環境に依存すると結論付けた.Airborne bacterial and fungal numbers in the buildings of Syowa Station in Antarctica were examined for 9 months in 2001. The number concentrations of bacteria and fungi were less than 20 and 70 CFU/m^3, respectively, in the dining room and washroom. The average number concentrations of bacteria and fungi were less than 1/50 or 1/5 of those in Japan and Europe, respectively, and remained constant regardless of season. The number concentrations of airborne microorganisms appeared to depend on drying of the indoor environment by the use of heaters

Fibulin-5 Contributes to Microfibril Assembly in Human Periodontal Ligament Cells

The elastic system fibers comprise oxytalan, elaunin and elastic fibers, which differ in their relative microfibril and elastin content. Human periodontal ligaments (PDL) contain only oxytalan fibers (pure microfibrils) among them. Since fibulin-5 regulates the organization of elastic fibers to link the fibers to cells, we hypothesized that fibulin-5 may contribute to the formation of oxytalan fibers. We used siRNA for fibulin-5 in PDL cell culture to examine the extracellular deposition of fibrillin-1 and -2, which are the major components of microfibrils. Fibulin-5 was labeled on microfibrils positive for fibrillin-1 and -2. Fibulin-5 suppression reduced the level of fibrillin-1 and -2 deposition to 60% of the control level. These results suggest that fibulin-5 may control the formation of oxytalan fibers, and play a role in the homeostasis of oxytalan fibers

Nivolumab-induced IgA nephropathy in a patient with advanced gastric cancer A case report

Introduction: Immune checkpoint inhibitors including nivolumab, an antibody against programmed death-1, have been increasingly introduced in various cancer treatment regimens, and are reported to be associated with immune-related adverse events. Nivolumab-induced renal injury is generally caused by acute interstitial nephritis and is managed by drug discontinuation and steroid therapy. Although this agent can infrequently induce glomerulonephritis, the pathogenesis and therapeutic strategy remain undetermined. Patient concerns: A 78-year-old man was diagnosed with advanced gastric cancer with portal thrombosis. First- and second-line chemotherapies were ineffective; thus, nivolumab monotherapy was initiated. Although it effectively prevented tumor growth, proteinuria and microhematuria appeared 2 months later. Despite drug discontinuation, serum creatinine progressively increased from 0.72 to 1.45 mg/dL. Renal biopsy revealed mesangial IgA and C3 deposition in immunofluorescence analysis and mesangial proliferation with crescent formation in light microscopy. Diagnosis: The patient was diagnosed with IgA nephropathy. Based on the temporal relationship between the nivolumab therapy and abnormal urinalysis, IgA nephropathy was considered to have been induced by nivolumab. Interventions: A moderate dose (0.6 mg/kg/day) of prednisolone was orally administrated, with tapering biweekly. Outcomes: Steroid therapy stabilized his serum creatinine levels and markedly reduced proteinuria. However, bacterial pneumonia substantially impaired his performance status; thus, nivolumab could not be restarted despite tumor regrowth. Lessons: IgA nephropathy should be recognized as an uncommon renal adverse event during nivolumab therapy. After drug discontinuation, nivolumab-induced IgA nephropathy is likely to respond to moderate doses of steroid therapy with early tapering. However, more evidence is needed to determine whether nivolumab can be safely restarted during or after steroid therapy

On the Surface Cracking and Crack Growth Due to the Oscilated Tangential Force without Macro Slip

The occurance of surface cracking in the contact field without any macro slip has been investigated. The effects of the static normal load and the range of alternating tangential force on the crack initiation and growth have been made clear. It was also shown that the stress field may be useful to estimate the total effects of the applied forces even on the surface cracking and growth